The present invention relates to a method of treatment and/or prophylaxis of irritable bowel syndrome (IBS) and irritable bowel disease (IBD).
IBS is a medical condition in which the gut functions improperly because of increased sensitivity to pain and abnormal movements. Symptoms may include abdominal discomfort or pain, often in association with urgency and diarrhea and/or constipation; bloating, spasms and painful cramping. Some hypersensitivity can be triggered by inflammation, as seen in dysentery. Colonic inflammation in can be prolonged by emotional stress.
IBD, this is also referred to as, Crohns and Colitis is a disorder involving inflammation and possible ulceration of the digestive tract. Symptoms include diarrhea, fever, anorexia, weight loss, gas, and abdominal tenderness. There may be bloody diarrhea if intestinal bleeding occurs.
It has been hypothesised that there may be an autoimmune component to both IBS and IBD where the immune system may react to the digestive cells as they break down, or food particles and bacteria that cross from the damaged intestinal walls into the blood stream. Although IBD does have similar symptoms to IBS, the cause may often be the result of an autoimmune disorder or an allergy to certain foods.
In both cases, the condition is known for inhibiting a person""s social interaction and loss of dignity. Indeed some people are prevented from leaving their houses or must conduct their affairs so as to be close to a place to relieve oneself.
The present invention has surprisingly determined that the administration (particularly by ingestion) of cetyl myristate, and particularly cetyl myristate in conjunction with cetyl palmitate, provides an effective treatment of IBD and/or IBS.
Cetyl myristate and cetyl palmitate can each be sourced from animals or vegetables. Cetyl myristate is not to be mistaken for cetyl myristoleate which is a fatty acid derived traditionally from spermaceti by saponification and more recently from the tallow of bovine(s).
Reference is made to U.S. Pat. No. 4,113,881 where it is disclosed that the administration of an effective amount of cetyl myristoleate to a mammal is useful in inhibiting or relieving the symptoms of inflammatory rheumatoid, arthritis in mammals. Also in U.S. Pat. No. 5,569,676 there is disclosure of the use of cetyl myristoleate in the treatment of osteo-arthritis.
It is thought that cetyl myristate has a negligible anti-arthritic activity in laboratory experiments and reference is made to the website www.gcinutrients.com/Newletter.com. However this point is arguable and a product known as cetyl myristate sold by Amerex Corporation of 770 Sycamore Avenue, Suite J148, Vista, Calif. 92083, USA purports that cetyl myristate is useful for the treatment of arthritis.
Cetyl myristate is derived from the saturated fatty acid, myristic acid. This acid is found in nutmeg butter, in the fats of Myristicaceae, in palm seed fats, milk fats and also sperm whale oil. Reference is made to U.S. Pat. No. 2,481,365 which discloses the preparation of myristic acid from tall-oil fatty acids. It is to be noted that Amerex Corporation source cetyl myristate used in their products from sunflower oil. See their website at www.hollinet.com.
Cetyl palmitate is derived from the fatty acid, palmitic acid which occurs as the glycerol ester in many oils and fats such as palm oil or Chinese vegetable tallow. A synthetic method of preparation is to react palmitoyl chloride and cetyl alcohol in the presence of magnesium. See the Merck Index, 12th edition at page 336. Reference is also made to U.S. Pat. No. 3,169,099 which discloses a biosynthetic method of producing cetyl palmitate.
As indicated earlier the present invention is directed to the treatment and/or prophylaxis of irritable bowel syndrome (IBS) and/or irritable bowel disease (IBD) reliant upon administration (whether by self administration or otherwise) of either cetyl myristate or cetyl myristate and cetyl palmitate (whether given simultaneously in admixture or not or given serially).
The present invention also encompasses the prospect of dosage forms that in some instances might contain cetyl myristate alone and in other instances both cetyl myristate and cetyl palmitate and dosage regimes that might use one dosage form or both.
In another aspect the invention is a method of treatment and/or prophylaxis of a mammal for irritable bowel syndrome and/or for irritable bowel disease which comprises or includes administering or having self administered to such mammal an effective amount of either
(a) cetyl myristate, or
(b) cetyl myristate and cetyl palmitate.
Preferably said administration is orally of (b) whether as a mixture of both cetyl myristate and cetyl palmitate, or serially.
Preferably the effective amount is of (b).
Preferably said administration is with a mixture of cetyl myristate in conjunction with cetyl palmitate where the cetyl myristate comprises from 50 to 98% w/w of the mixture.
Preferably said effective amount of (a) or (b) is by means of one or more capsules.
In one type of use said mammal is a human being suffering from irritable bowel syndrome and the administration is for treatment purposes.
In another type of use said mammal is a human being suffering from irritable bowel disease and the administration is for treatment purposes.
In another aspect the invention is an oral pharmaceutical composition for treating irritable bowel syndrome which comprises or includes both cetyl myristate and cetyl palmitate.
In still another aspect the invention is an oral pharmaceutical composition for treating irritable bowel disease which comprises or includes both cetyl myristate and cetyl palmitate.
Preferably said cetyl myristate comprises at least 50% by weight of the composition.
Preferably said composition also includes at least one pharmaceutically acceptable excipient and/or diluent.
In still another aspect the invention is an oral dosage unit effective in the treatment of irritable bowel syndrome and/or irritable bowel disease, said dosage unit having either
(a) cetyl myristate, or
(b) a mixture of cetyl myristate and cetyl palmitate.
Preferably said dosage unit has (b) and said cetyl myristate in any such mixture comprises from 50 to 98% w/w of the mixture.
In another variant the dosage unit has (a) only and there is between 5 to 400 mg of cetyl myristate.
Preferably in the dosage use, where (b) is present, there is from 5 to 400 mg of the mixture of cetyl myristate and cetyl palmitate.
Preferably (a) or (b) is in a capsule.
Preferably said capsule also includes a pharmaceutically acceptable excipient and/or diluent.
Preferably the dosage unit includes silicon dioxide.
Preferably the dosage unit also contains calcium phosphate and/or magnesium oxide.
Preferably the dosage unit also includes additionally at one trace element.
In another aspect the invention is the use, in the manufacture of oral dosage units for the treatment or prophylaxis of irritable bowel disease in a mammal, of
(a) cetyl myristate, or
(b) a mixture of cetyl myristate and cetyl palmitate, or
(c) cetyl palmitate.
In another aspect the invention is the use, in the manufacture of oral dosage units for the treatment or prophylaxis of irritable bowel syndrome in a mammal, of
(a) cetyl myristate or
(b) cetyl myristate and cetyl palmitate or,
(c) cetyl palmitate.
The mixture can use cetyl myristate available from a commercial source such as EHP Products Inc., PO Box 20727, Mt Pleasant, S.C. 29465 or at Amerex Corporation, 770 Sycamore Avenue Suite J148 Vista, Calif. 92083.
The mixture can use cetyl palmitate derived from a source such as, for example, Quimica Croda, S. A. de C. V, Circuito Mxc3xa9dicos No.47. Apdo. Postal 71-A Cd. Satxc3xa9lite, 53100 Naucalpan, Edo. de Mxc3xa9xico, Mxc3xa9xico or online at www.butterburandsage.com.
Most ideally however the mixture is synthetised from starting materials utilising the procedures as disclosed in New Zealand Patent Specification No. 332959 which involves reacting both myristic acid and palmitic acid with a cetyl alcohol at an elevated temperature in the presence of at least one acid catalyst and at least one aromatic hydrocarbon. The aromatic hydrocarbon fraction then contains the cetyl myristate and cetyl palmitate from whence it can be crystallised.
The full content of NZ 332959 is here incorporated by way of reference.
This crystallised form can then be ground up, dissolved and mixed with a suitable general pharmacy liquid to be administered to a person. The crystals are usually dissolved in hot water before adding to the pharmacy liquid which is usually a sugar syrup available from most pharmaceutical companies. The liquid is made up to a concentration of 70 w/v.
Alternatively the crystals may be ground up into a powder and combined with magnesium oxide, silicon oxide and fine di-calcium phosphate. This powder can then be transferred into capsules for oral ingestion into the body. The capsules used are VEGICAP(trademark) that are non-gelatin containing.
The mode of administration is preferably oral. The dosage unit can be either a swallowable capsule or some alternative (preferably having the active ingredient(s) as a wax-like solid or can be an orally consumable liquid composition (eg; made up with a general pharmacy type carrier such as methyl cellulose)).
Other modes of administration can include transdermal and suppository delivery (the latter being generally contraindicated having regard to the targeted condition).
The administration process preferably involves either orally ingesting capsules or drinking the liquid formulation either on an empty stomach or not. The number of capsules or liquid taken depends on the size and severity of the persons condition.
Generally, an adult suffering from Irritable Bowel Syndrome should to take at least 4 capsules 3 times daily of a preferred dosage unit as herein described for a period of at least six to eight weeks. The doses can then be reduced to suit the individual. Whereas for a child the number of capsules taken is reduced to half or less. This dosage may be increased or decreased depending on whether the symptoms begin to clear up.
Similarly for the liquid formulation, where an amount of liquid equivalent to at least 4 capsules is prescribed which is to be taken 3 times daily. That is 4200 mg of cetyl myristate or the mixture of cetyl myristate and cetyl palmitate.
The administration process for the Irritable Bowel Disease involves initially ingesting a substantially less amount of the dosage unit effective for treating irritable bowel syndrome. It is suggested that the dose for adults and children is one 11 milligram capsule of the dosage unit as described in the invention on a daily basis for 2 or 3 weeks. The dosage rate is then increased to one 11 milligram dosage unit twice daily for 2 or 3 weeks which continues on for a further 6 to 8 weeks.
Following such a dosage rate for Irritable Bowel Disease the benefits do take time and are usually noticeable after the first three weeks of taking the said invention.
The action of the abovementioned invention can be measured through mediator relief from granulocytes and lymphocytes. Non Ig-E mediated reactions can be detected in the components of the circulating immune cells regardless of mechanism or pathway by detecting the common end point, this being a mediator release from circulating immune cells.
The use of the invention with individual diets can reduce inflammation and reactive factors of a person to a point where allergies and previous allergic reaction do not occur. This can also include reducing the reactivity to certain food intolerance.
Trials with a variety of patients reliant upon dosage forms of cetyl myristate alone have shown favorable responses insofar as relief from the symptoms of IBS and/or IBD are concerned. It has been found however that enhanced benefits occur where there is at least a small proportion of cetyl palmitate in addition to the cetyl myristate and it is to the use of one such ratio of these active ingredients that the following trial examples relate.
Examples of use follows. Each briefly describes the patient""s condition before and after the stated treatment using dosage forms (ie; xe2x80x9cof the inventionxe2x80x9d) each having about 350 mg of the mixture of cetyl myristate and cetyl palmitate. That mixture comprises by weight 95% cetyl myristate and 5% cetyl palmitate by weight manufactured by the process as disclosed in NZ Patent Specification No. 332959. In addition added excipients were present in the non-gelatin two part capsule case.